Donidalorsen

In Tryngolza, Ionis is hoping to break the blockbuster ceiling for the first time with a wholly owned product. Credit: Shutterstock/Cagkan Sayin.com. Earlier this year, Ionis’ CEO Brett Monia said that Tryngolza (olezarsen) would become the company’s first fully owned blockbuster drug, with that forecast having just become more likely following a US label expansion. The US Food and Drug Administration (FDA) has approved Tryngolza as an adjunct to diet to reduce triglycerides (TG) and the risk of acute pancreatitis in adults with severe hypertriglyceridemia (sHTG). With the label update, Tryngolza, which was already approved for the rare disease familial chylomicronemia syndrome (FCS), becomes the only approved targeted medication shown to improve pancreatitis in sHTG patients. sHTG is characterised by an increased risk of pancreatic inflammation, which causes pain and can lead to hospitalisation due to life-threatening organ damage. Around three million people in the US have sHTG, one million of whom are considered at high risk of complications. The FDA approval was based on positive results from the Phase III CORE and CORE2 studies, which were published in The New England Journal of Medicine . In the studies, Tryngolza cut fasting triglyceride levels by up to 72% compared to placebo at six months. These benefits were sustained after a year. Additionally, Ionis’ drug significantly reduced acute pancreatitis events by up to 91%. Among patients treated with Tryngolza, 86% achieved triglyceride levels below 500 mg/dL – a critical threshold for reducing acute pancreatitis risk. Tryngolza is an apoC-III antisense oligonucleotide (ASO) that blocks the production of apolipoprotein C-III (apoC-III), a protein that inhibits the breakdown and clearance of triglycerides in the blood. The medication is self-administered once monthly via an autoinjector. Monia commented: “The approval marks an historic advance for people who have long struggled to control their dangerously high triglycerides, providing the only approved therapy for sHTG to dramatically lower triglyceride levels and significantly reduce acute pancreatitis events.” “As our first independent launch in a prevalent disease, this milestone builds on our success in familial chylomicronemia syndrome, a rare form of sHTG, and marks a defining moment for Ionis as we bring our groundbreaking medicines to even more patients in need,” Monia added. Ionis embarks on blockbuster road As well as Tryngolza, Ionis has another marketed drug in a rare disease. Dawnzera (donidalorsen), an RNA-targeted therapy, is FDA approved for the prevention of hereditary angioedema (HAE) attacks. Ionis does have three other therapies commercialised via partnerships. The most well-known of these is Biogen-partnered Spinraza (nusinersen), the first approved treatment for spinal muscular atrophy (SMA). Spinraza generated $1.55bn in sales in 2025. With Tryngolza, Ionis is hoping to break the blockbuster ceiling for the first time via a wholly owned product. Speaking at the J.P. Morgan Healthcare Conference in January this year, Monia revealed Ionis had increased Tryngolza’s peak revenue forecasts based on an sHTG approval. With the FDA authorisation now secured, that peak sales target of $2bn looks within reach. GlobalData’s Pharma Intelligence Centre predicts global sales of $1.7bn in 2032. GlobalData is the parent company of Pharmaceutical Technology . Citi analysts commented in a research note: “While near-term competitor pivotal data are worth monitoring as an incremental hurdle to Ionis sentiment, we continue to see Tryngolza positioning benefiting from a material first-mover advantage.” Investors will be keeping an eye on a readout from Arrowhead’s Phase III SHASTA-3 and SHASTA-4 trials of plozasiran for sHTG treatment expected in Q3.